Table 2.

The list of multi-target therapeutics and the key biological activity.

Multi-target therapeutics	Chemical structure	Key biological activities	Reference
GO@Dau		•Neuroprotective activity •Reversed MDA and SOD level •Alleviated ROS level •Reduced apoptosis of SH-SY5Y cells •Improved neurocognitive deficits and anxiety-like behaviors •Restored damaged neurons •Reduced activation of astrocytes and microglia	[99]
Tetrahydroisoquinoline-benzimidazole		•Inhibition of neuroinflammation and BACE1 •Enhanced anti-neuroinflammatory activity •Reduced glutamate-induced cytotoxicity •ROS reduction •Increased GSH level •Able to penetrate BBB	[110]
Tetrahydroisoquinoline-oxoisoaporphine		•Good anti-inflammatory activity and anti-Aβ aggregation potency •Neuroprotective activity	[111]
Tryptophan-tetrahydroisoquinoline		•Selective inhibitor of BChE •Inhibited self-aggregation of Aβ peptides •Neuroprotective effect from Aβ-induced cell death •Reversed Aβ-induced cognitive dysfunctions in mouse •Able to penetrate BBB	[11]
Tetrahydroisoquinoline-cinnamic acid		•Decreased activity of huBuChE •Inhibition of MAO-A and MAO-B •Good antioxidant potency and anti-inflammatory activity •Inhibition of self-induced Aβ42 aggregation •Neuroprotective effect against SH-SY5Y •Good BBB permeability via passive diffusion •Good stability in artificial gastric fluid and artificial intestinal fluid •Improved scopolamine-induced memory impairment	[130]